Association of Lifestyle and Genetic Risk With Incidence of Dementia.
Level 3 - non-randomized controlled study
Retrospective cohort study using UK Biobank data
PubMed 31302669 · doi:10.1001/jama.2019.9879
What was done
A retrospective cohort study analyzed 196,383 participants of European ancestry aged 60 years or older without cognitive impairment or dementia at baseline from the UK Biobank (enrolled 2006–2010, followed until 2016–2017; median follow-up 8.0 years, total 1,545,433 person-years). Genetic risk was categorized into low (lowest quintile), intermediate (quintiles 2–4), and high (highest quintile) using a polygenic risk score. Lifestyle was categorized into favorable (68.1%), intermediate (23.6%), and unfavorable (8.2%) based on smoking, physical activity, diet, and alcohol intake. The primary outcome was incident all-cause dementia ascertained via hospital inpatient and death records.
What was found
Participants with high genetic risk had a higher dementia incidence (1.23% [95% CI, 1.13%–1.35%]) than those with low genetic risk (0.63% [95% CI, 0.56%–0.71%]; adjusted HR, 1.91 [95% CI, 1.64–2.23]). Participants with high genetic risk and an unfavorable lifestyle had a 1.78% (95% CI, 1.38%–2.28%) incidence compared to 0.56% (95% CI, 0.48%–0.66%) in those with low genetic risk and a favorable lifestyle (HR, 2.83 [95% CI, 2.09–3.83]). There was no significant interaction between genetic risk and lifestyle (P = .99). Among participants with high genetic risk, a favorable lifestyle was associated with a significantly lower risk of dementia compared to an unfavorable lifestyle (1.13% vs 1.78%; HR, 0.68 [95% CI, 0.51–0.90]).
Why it matters
The findings demonstrate that adopting healthy lifestyle behaviors is associated with a lower incidence of dementia even among individuals at high polygenic risk, suggesting genetic risk does not completely dictate disease risk.
Limits
The study was restricted to participants of European ancestry, limiting generalizability to other racial and ethnic groups. Dementia ascertainment relied on electronic health records (hospitalizations and mortality) rather than active standardized cognitive assessments, which likely undercounted less severe or non-hospitalized cases. Lifestyle factors were self-reported at baseline, introducing potential reporting bias and inability to account for lifestyle changes over time.
Cited by
- supports Multiple studies show that high polygenic disease risk can be neutralized by adopting healthy lifestyle factors.